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Frontotemporal dementia (FTD) affects behavior, language, and personality. This study aims to explore functional connectivity changes in three FTD variants: behavioral (bvFTD), semantic (svPPA), and nonfluent variant (nfvPPA). Seventy-six patients diagnosed with FTD by international criteria and thirty-two controls were investigated. Functional connectivity from resting functional magnetic resonance imaging (fMRI) was estimated for the whole brain. Two types of analysis were done: network basic statistic and topological measures by graph theory. Several hubs in the limbic system and basal ganglia were compromised in the behavioral variant apart from frontal networks. Nonfluent variants showed a major disconnection with respect to the behavioral variant in operculum and parietal inferior. The global efficiency had lower coefficients in nonfluent variants than behavioral variants and controls. Our results support an extensive disconnection among frontal, limbic, basal ganglia, and parietal hubs.

Neurodegenerative diseases comprise a wide variety of mental symptoms whose evolution is not directly related to the visual analysis made by radiologists, who can hardly quantify systematic differences. Moreover, automatic brain morphometric analyses, that do perform this quantification, contribute very little to the comprehension of the disease, i.e., many of these methods classify but they do not produce useful anatomo-functional correlations. This paper presents a new fully automatic image analysis method that reveals discriminative brain patterns associated to the presence of neurodegenerative diseases, mining systematic differences and therefore grading objectively any neurological disorder. This is accomplished by a fusion strategy that mixes together bottom-up and top-down information flows. Bottom-up information comes from a multiscale analysis of different image features, while the top-down stage includes learning and fusion strategies formulated as a max-margin multiple-kernel optimization problem. The capacity of finding discriminative anatomic patterns was evaluated using the Alzheimer's disease (AD) as the use case. The classification performance was assessed under different configurations of the proposed approach in two public brain magnetic resonance datasets (OASIS-MIRIAD) with patients diagnosed with AD, showing an improvement varying from 6.2% to 13% in the equal error rate measure, with respect to what has been reported by the feature-based morphometry strategy. In terms of the anatomical analysis, discriminant regions found by the proposed approach highly correlates to what has been reported in clinical studies of AD.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) and semantic variant (svPPA) of frontotemporal dementia (FTD) are neurodegenerative diseases. Previous works have shown alterations of fractional anisotropy (FA) and mean diffusivity (MD) from diffusion tensor images (DTIs). This manuscript is aimed at using DTI images to build a global tractography and to identify atrophy patterns of white matter in each variant. Twenty patients with svPPA, 20 patients with nfvPPA, 26 patients with behavioral variant of FTD (bvFTD) and, 33 controls were included. An analysis based on the connectivity of structural networks showed changes in FA and MD in svPPA and nfvPPA with respect to bvFTD. Much damage in the internal networks of the left temporal lobe was found in svPPA patients; in contrast, patients with nfvPPA showed atrophy in networks from the basal ganglia to motor and premotor areas. Those findings support the dual stream model of speech and language.

In magnetic resonance imaging (MRI), accuracy and precision with which brain structures may be quantified are frequently affected by the partial volume (PV) effect. PV is due to the limited spatial resolution of MRI compared to the size of anatomical structures. Accurate classification of mixed voxels and correct estimation of the proportion of each pure tissue (fractional content) may help to increase the precision of cortical thickness estimation in regions where this measure is particularly difficult, such as deep sulci. The contribution of this work is twofold: on the one hand, we propose a new method to label voxels and compute tissue fractional content, integrating a mechanism for detecting sulci with topology preserving operators. On the other hand, we improve the computation of the fractional content of mixed voxels using local estimation of pure tissue intensity means. Accuracy and precision were assessed using simulated and real MR data and comparison with other existing approaches demonstrated the benefits of our method. Significant improvements in gray matter (GM) classification and cortical thickness estimation were brought by the topology correction. The fractional content root mean squared error diminished by 6.3% (p<0.01) on simulated data. The reproducibility error decreased by 8.8% (p<0.001) and the Jaccard similarity measure increased by 3.5% on real data. Furthermore, compared with manually guided expert segmentations, the similarity measure was improved by 12.0% (p<0.001). Thickness estimation with the proposed method showed a higher reproducibility compared with the measure performed after partial volume classification using other methods.

The goal of this paper is to evaluate the suitability of a bag-of-feature representation for automatic classification of Alzheimer's disease brain magnetic resonance (MR) images. The evaluated method uses a bag-of-features (BOF) to represent the MR images, which are then fed to a support vector machine, which has been trained to distinguish between normal control and Alzheimer's disease. The method was applied to a set of images from the OASIS data set. An exhaustive exploration of different BOF parameters was performed, i.e. feature extraction, dictionary construction and classification model. The experimental results show that the evaluated method reaches competitive performance in terms of accuracy, sensibility and specificity. In particular, the method based on a BOF representation outperforms the best published result in this data set improving the equal error classification rate in about 10% (0.80 to 0.95 for Group 1 and 0.71 to 0.81 for Group 2).

's diseaseMagnetic resonance (MR) provides a non--invasive way to investigate changes in the brain resulting from aging or neurodegenerative disorders such as Alzheimer's disease (AD). Performing accurate analysis for population studies is challenging because of the interindividual anatomical variability. A large set of tools are found to perform studies of brain anatomy and population analysis (FreeSurfer, SPM, FSL). In this paper we present a newly developed surface--based processing pipeline (milxCTE) that allows accurate vertex--wise statistical comparisons of brain modifications, such as cortical thickness (CTE). The brain is first segmented into the three main tissues: white matter, gray matter and cerebrospinal fluid, after CTE is computed, a topology corrected mesh is generated. Partial inflation and non--rigid registration of cortical surfaces to a common space using shape context are then performed. Each of the steps was firstly validated using MR images from the OASIS database. We then applied the pipeline to a sample of individuals randomly selected from the AIBL study on AD and compared with FreeSurfer. For a population of 50 individuals we found correlation of cortical thickness in all the regions of the brain (average r =0.62 left and r =0.64 right hemispheres). We finally computed changes in atrophy in 32 AD patients and 81 healthy elderly individuals. Significant 2 differences were found in regions known to be affected in AD. We demonstrated the validity of the method for use in clinical studies which provides an alternative to well established techniques to compare different imaging biomarkers for the study of neurodegenerative diseases.

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